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The Journal of Immunology, Vol 143, Issue 12 3894-3900, Copyright © 1989 by American Association of Immunologists


ARTICLES

The mechanisms of antibody-dependent killing mediated by lymphoid and myeloid cells are distinct based on different divalent cation requirements

RF Graziano, DV Erbe and MW Fanger
Department of Microbiology, Dartmouth Medical School, Hanover, NH 03756.

To further understand the mechanism(s) of antibody-dependent cell- mediated cytotoxicity (ADCC) by various effector populations, we have examined the extracellular Ca++ and Mg++ requirements for ADCC performed by lymphocytes, monocytes, polymorphonuclear leukocytes and peritoneal macrophages. We have used the anti-Fc gamma R-bearing hybridoma cell lines (HC) as self directed targets for ADCC to analyse the triggering ability of each of the three defined Fc gamma R; Fc gamma RI, Fc gamma RII, and Fc gamma RIII. Lymphocyte killing of the anti-Fc gamma RIII bearing HC (HC 3G8) was Ca++ dependent, but Mg++ independent. In contrast, monocytes and PMN killed the anti-Fc gamma RI- (HC 32) and the anti-Fc gamma RII- (HC IV.3) bearing HC in a Mg++- dependent, Ca++-independent fashion. In addition, freshly prepared monocytes were able to kill HC 3G8 in a Mg++-dependent, Ca++- independent fashion, indicating that low levels of Fc gamma RIII may be functionally detected on monocytes. Peritoneal macrophages were able to kill all three of the anti-Fc gamma R bearing HC in a Mg++-dependent, Ca++-independent fashion. Thus, the same target is lysed by myeloid cells in the presence of Mg++ without Ca++ and by lymphoid cells in the presence of Ca++ without Mg++. These results suggest that at least two distinct mechanisms of ADCC exist that depend on the type of effector cell mediating antibody-dependent killing and not necessarily on the Fc gamma R type triggered.


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